Diketo-dicarboxylic acids and salts and preparation thereof by alkaline oxidation



United States Patent 3,441,605 DIKETO-DICARBOXYLIC ACIDS AND SALTS ANDPREPARATION THEREOF BY ALKALINE OXIDATION Stephen Blake, Fullwood,Preston, England, assignor, by mesne assignments, to Wallace & Tiernanlnc., East Orange, N.J., a corporation of Delaware No Drawing. FiledFeb. 15, 1966, Ser. No. 527,474 Claims priority, application GreatBritain, Feb. 17, 1965, 6,745/ 65 Int. Cl. C07c 55/02, 49/12, 49/30 US.Cl. 260537 6 Claims ABSTRACT OF THE DISCLOSURE Novel diketo-dicarboxylicacids useful as polyvinyl chloride plasticizers are provided having theformula R CO-(CHmH-COOH (CHz)4 CO-(CH2)4(|3H-COOH wherein the groups Rare the same and each is H or CH The compounds of Formula I are preparedby process which comprises hydrolyzing a tetraketone having the Thetetraketones of Formula II are novel and are produced by a process whichcomprises reacting adipoyl dichloride with an excess over thestoichiometric proportion of an enamine of a cyclohexanone, thecyclohexanone having the formula The present invention relates to theproduction of organic acids and ketones and in particular to theproducwherein the groups R are the same and each is H or CH andcarboxylic salts and esters thereof.

The present invention also provides a process of producing adiketo-dicarboxylic acid having the Formula I ice which compriseshydrolyzing a tetraketone having the formula:

wherein the groups R are the same and each is H or CH The invention alsocomprises the tetraketones of Formula II which are also new compounds.

The process of producing the diketo-dicarboxylic acid (I) is carriedout, for example, by heating the tetraketone with aqueous alkali at atemperature suificient to cleave both of the ring structures in themolecule of the tetraketone to produce the correspondingdiketo-dicarboxylic acid. Preferably, the alkali is a solution of analkali metal hydroxide. The process can be carried out using pure orsubstantially pure tetraketone, but more conveniently, the startingmaterial may be the crude or partially purified tetraketone produced ina previous process, for instance by the reaction of an enamine ofcyclohexanone or an enamine of a substituted cyclohexanone with adipoyldichloride as hereinafter described. The hydrolysis of the tetraketonecan be effected, for example, by heating the tetraketone ortetraketone-containing starting material with an aqueous alkali metalhydroxide solution at an elevated temperature, conveniently at theboiling point of the mixture under reflux conditions, but moreadvantageously at a lower temperature, for instance at a temperature ofless than 40 C., for a suflicient time to cleave the tetraketone toyield the diketo-dicarboxylic acid. The reaction product may then betreated with an acid in a proportion at least sufficient to neutralisethe excess alkali and so produce the free diketo-dicarboxylic acid.

The present invention also provides a process of producing a tetraketone(II) which comprises reacting adipoyl dichloride with an excess over thestoichiometric proportion of an enamine of a cyclohexanone, thecyclohexanone having the formula:

(311 OH; C

wherein the group R is H or CH The adipoyl dichloride employed in theprocess is prepared, for example, from adipic acid by any per seconcentional method for producing acyl chloride from the correspondingcarboxylic acid.

The enamine of a cyclohexanone, (III) which is used in the process ofproducing a tetraketone (II) is preferably an enamine derived from adecondary amine. It is particularly preferred to use an enamine derivedfrom a cyclohexanone (III) and a secondary cyclic amine, for example,morpholine. The adipoyl dichloride is preferably reacted with at leastfour molar proportions of the secondary amine enamine per molarproportion of the dichloride, so that there is at least sufiicient ofthe enamine base present in the reaction mixture to bind the hydrogenchloride produced by the reaction. In this way it is not necessary tohave present a hydrogen chloride-binding agent in addition to theenamine base present as a reactant, although an added binding agent maybe present if desired.

The reaction of the adipoyl dichloride with the secondary amine enamineof the cyclohexanone to produce the tetraketone is carried out in anoragnic solvent, for instance dioxan, benzene or toluene, or otherorganic Sol- (III) 3 vent which behaves similarly under the reactionconditions.

The reaction may be conveniently effected by slowly adding a solution ofadipoyl dichloride in dry dioxan, with stirring, to a solution of theenamine of the cyclohexanone also in dry dioxan, subsequently stirringthe mixture for a further period of time before boiling the mixtureunder reflux conditions for an extended period. The reaction mixture isthen cooled and the hydrochloride of the enamine of the cyclohexanonewhich separates, filtered off and washed with dioxan. The filtratetogether with washings is then hydrolyzed with mineral acid, forinstance with dilute hydrochloric acid, and the mixture boiled underreflux conditions. The tetraketone product is then isolated bydistilling oi the dioxan solvent, extracting the distillation residuewith a suitable organic solvent, for example diethyl ether, washing thesolution free from acid, drying the solution and removing the solvent bydistillation. If desired, the tetraketone product can be furtherpurified for instance by recrystallization from a suitable solvent suchas ethylacetate.

The diketo-dicarboxylic acids and the tetraketones of the invention canbe used as intermediates in the production of other organic compounds.The diketo-dicarboxylic acids are also useful, in the form of theiralkyl esters, as plasticizers for vinyl chloride polymers or copolymersthereof and be used as cross-linking agents in the production ofsynthetic polymeric materials.

The following examples further illustrate the present invention. Partsby weight shown therein bear the same relation to parts by volume as dokilograms to liters. Percentages are expressed by weight unlessotherwise stated.

Example 1 92 parts by weight of adipoyl dichloride in 350 parts byvolume of dry dioxan were slowly added to a stirred solution of 336parts by weight of l-rnorpholino-cyclohexl-ene in 1600 parts by volumeof dioxan over a period of 60 minutes. When addition of the adipoyldichloride was completed, the resulting mixture was stirred for afurther period of 2 hours and the mixture was then boiled under reflux,with stirring, for hours. The resulting product was cooled and thel-morpholino-cyclohex-l-ene hydrochloride formed was filtered oil. Thesolid was washed with dioxan. 680 parts by volume of 10% hydrochloricacid were added to the combined filtrate and washings and the mixturewas boiled under reflux for 2 hours.

Dioxan was then removed by distillation at subatmospheric pressure andthe residue was extracted with diethyl ether. The ethereal solution waswashed with aqueous potassium bicarbonate solution and dried overanhydrous sodium sulphate. The ether was removed by distillation andafter recrystallization of the semi-solid residue from ethyl acetate,there remained 37 parts by weight of 1,6-bis(2-oxocyclohexyl)hexane-1,6-dione having melting point 89 to 93 C. Afterfurther recrystallization from ethyl acetate, a sample was obtained withmelting point 93 to 95 C. and the following elemental analysis:

Found: carbon, 70.26%; hydrogen, 8.34%. Calculated: carbon, 70.55%;hydrogen, 8.56%.

Example 2 The tetraketone 1,6-bis(2-oxocyclohexyl)hexane-1,6- dione wasprepared by the procedure described in the first paragraph of Example 1.

Dioxan was then removed from the resulting mixture by distillation atsubatmospheric pressure and the residue was heated to 100 C. 460 partsby volume of hot 135% aqueous potassium hydroxide solution were addedand the resulting mixture was heated for 5 minutes at 100 C. The productwas then poured into a large excess of water, and washed with ether;excess hydrochloric acid was added in a proportion suflicient toneutralize the potassium hydroxide added and the mixture was allowed tostand for 10 hours. The crude 7,12-dioxo-octadecane-1,18-dioic acidproduced was filtered off and recrystallised from ethyl acetate. Theproduct had melting point 124 to 126 C. and the following elementalanalysis:

Found: carbon, 63.41%; hydrogen, 8.8%. Calculated: carbon, 63.14%;hydrogen, 8.83%.

Example 3 A solution of 32.2 parts by weight of adipoyl dichloride in120 parts by volume of dry dioxan was added to a stirred solution of 127parts by weight of 1-morpho1ino-6- methylcyclohex-l-ene in 600 parts byvolume of dry dioxan over 30 minutes in atmosphere of dry nitrogen. Themixture was stirred at 15 C. for 1 hour and then refiuxed for 10 hours.The solid was filtered off and washed with dioxan, the dioxan washingswere then combined with the dioxan filtrate.

The whole dioxan solution was treated with 10% aqueous hydrochloric acidand refluxed for 2 hours. The solvents were then distilled off to giveparts by weight of a semi-solid product containing1,6-bis(2-oxo-3-methylcyclohexyl)-hexane-1,6-dione which could berecovered and purified by the procedure described in Example 1. To thismaterial, when cool, was added a solution of 88 parts by weight ofpotassium hydroxide in 64 parts by volume of water; the mixture was thenstirred for 4 hours at 15 C. 800 parts by volume of water were added andthe whole resulting mixture was extracted with ether. The aqueous layerobtained was acidified and again extracted with ether. The product wasobtained by distilling off the ether and recrystallizing first fromether and then from petroleum ether (boiling point range 60 to 80 C.),being 0.7 part by weight of 2,17-dimethyl-7,12-dioxooctadecane-LlS-dioicacid of melting point 92 to 93 C. and the following elemental analysis:

Found: carbon, 64.57%; hydrogen, 9.33%. Calculated (C H O carbon 64.85%;hydrogen, 9.25%.

Example 4 The tetraketone 1,6-bis(2-oxocyclohexyl)hexane-1,6- dione wasprepared by the procedure described in the first paragraph of Example 1.

Dioxan and water were then removed until the residue became a crudegranular solid. This solid was then added to a cool, stirred solution of260 parts by weight of potassium hydroxide in 190 parts by volume ofwater, the temperature being kept below 40 C. After stirring the mixturefor 4 hours, the solution was diluted by adding 1300 parts by volume ofwater and the diluted solution was filtered and acidified withconcentrated hydrochloric acid.

The product which was filtered off, dried and recrystallized from ethylacetate, was 7,12-dioxo-octadecane-1, 18-dioic acid having melting pointto 122 C. and the following elemental analysis:

Found: carbon, 62.97%; hydrogen, 8.64%. Calculated (C H O carbon,63.14%; hydrogen, 8.83%.

92 parts by weight of the crude product were obtained (representing ayield of 54% theoretical) and the purified product amounted to 5 6 partsby weight (representing a yield of 33%).

parts by weight of l-morpholino-cyclohex-l-ene hydrochloride wererecovered.

Example 5 A solution of adipoyl chloride (92 parts by weight) in drybenzene (350 parts by volume) was added to a stirred solution ofl-morpholinocyclohex-l-ene (336 parts by weight) in dry benzene (1600parts by volume) over a period of 60 minutes under dry nitrogen. Duringthe addition the temperature of the reactants rose from 16 to 30 C. Theresulting mixture was stirred for a further 2 hours, then boiled underreflux with stirring for 6% hours.

The resulting product was cooled and the l-morpholinocyclohex-l-enehydrochloride formed was filtered off and washed with benzene. Thesolvent on the combined filtrate and washings was removed by rotaryevaporation. The residue was dissolved in ethanol (250 parts by volume),water (250 parts by volume), concentrated hydrochloric acid (250 partsby volume), and the mixture was boiled under reflux for 2 /2 hours.

After this time the solution was cooled, the ethanol/ water was removedby distillation until the temperature of the boiling liquid was about100. The residue was cooled; a solid separated and was filtered off. Theliquor was then extracted with di-isopropyl ether (500 parts by volume).The ether extract was washed with water (500 parts by volume) then 250parts by volume of water was added, followed by sodium bicarbonate toneutralise and excess acid. The ether extract was finally washed againwith water (2X 200 parts by volume) and allowed to dry over anhydroussodium sulphate. The di-isopropyl ether was finally removed bydistillation to yield a light brown liquid (86 parts by weight).

This liquid was allowed to stand at C. and crystallized to a yellowgreasy solid, which was filtered to yield a pale yellow solid and abrown liquor. The solid was extracted with petroleum ether (B.P. 4060C.). The residue was substantially adipoylcyclohexanone (18.2 parts byweight). A sample of this product was recrystallized from ethyl acetatethree times to give pure adipoylcyclohexanone having melting point 9698C. and the following elemental analysis:

Found: carbon, 70.33%; hydrogen, 8.49%. Calculated: carbon, 70.55%;hydrogen, 8.56%.

A further 8.0 parts by weight of crude adipoylcyclohexanone crystallizedfrom the petroleum extract.

Example 6 A solution of adipoyl chloride (92 parts by weight) in drytoluene (350 parts by volume) was added to a stirred solution ofl-morpholinocyclohex-1-ene (336 parts by weight) in dry toluene (1600parts by volume) over a period of 60 minutes under dry nitrogen. Duringthe addition the temperature of the reactants rose from 16 to C. Theresulting mixture was stirred for a further 2 hours, then boiled underreflux with stirring for 6% hours.

The resulting product was cooled and the l-morpholinocyclohex-l-enehydrochloride formed was filtered off and washed with toluene. Thesolvent on the combined filtrate and washings was removed by rotaryevaporation. The residue was dissolved in ethanol (250 parts by volume),water (250 parts by volume), concentrated hydrochloric acid (250 partsby volume) and the mixture was boiled under reflux for 2 /2 hours.

After this time the solution was cooled, the ethanol/ water was removedby distillation until the temperature of the boiling liquid was about100 C. The residue was cooled; a solid separated and was filtered off.The liquor was then extracted with di-isopropyl ether (500 parts byvolume). The ether extract was washed with water (500 parts by volume),then 250 parts by volume of water was added followed by sodiumbicarbonate to neutralize any excess acid. The ether extract was finallywashed again with water (2X 200 parts by volume) and allowed to dry overanhydrous sodium sulphate. The diisopropyl ether was finally removed bydistillation to yield a brown liquid (63.7 parts by weight).

This liquid was allowed to stand at 0 C. and crystallized to a greasysolid, which was filtered to yield a pale brown solid and a dark brownliquor. The residue was washed with cold ethyl acetate to yield crudeadipoylcyclohexanone (9.5 parts by weight), a sample of which wasrecrystallized twice from ethyl acetate to yield adipoylcyclohexanonehaving melting point 9498 C.

What we claim is: 1. A diketo-dicarboxylic acid having the formula R lCO-(CHQtCH-COOH 2): oooHnir lu-ooou wherein the groups R are the sameand each is a member selected from the group consisting of H and CH andalkali metal salts thereof.

2. A diketo-dicarboxylic acid according to claim 1, wherein each R is H,said acid being 7,12-dioxo-octadecane-1,18-dioic acid.

3. A diketo-dicarboxylic acid according to claim 1, wherein each R is CHsaid acid being 2,17-dimethyl-7, 12-dioxo-octadecane-1,18-dioic acid.

4. A process of producing a diketo-dicarboxylic acid having the formulaR I CO'(CH2)4CH-C0oH CO(CHz)4(lJH-COOH wherein the groups R are the sameand each is a member selected from the group consisting of H and CHwhich comprises hydrolyzing a tetraketone having the formula:

References Cited UNITED STATES PATENTS 2,815,375 12/1957 Kamlet 260-5373,356,722 12/ 1967 Wallace et al. 260-537 JAMES A. PATTEN, PrimaryExaminer.

V. GARNER, Assistant Examiner.

US. Cl. X.R.

